Incidence, Clinical Features, and Prognostic Impact of CALR Exon 9 Mutations in Essential Thrombocythemia and Primary Myelofibrosis: An Experience of a Single Tertiary Hospital in Korea

We evaluated the incidence, clinical characteristics, and prognostic impact of calreticulin (CALR) mutations in essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients. In all, 48 ET and 14 PMF patients were enrolled, and the presence of CALR mutations was analyzed by direct sequencing. Patients were classified into three subgroups according to Janus kinase 2 (JAK2) V617F and CALR mutation status, and their clinical features and prognosis were compared. CALR mutations were detected in 15 (24.2%) patients, and the incidence increased to 50.0% in 30 JAK2 V617F mutation-negative cases. These included 11 patients with three known mutations (c.1092_1143del [seven cases], c.1154_1155insTTGTC [three cases], and c.1102_1135del [one case]) and 4 patients with novel mutations. ET patients carrying CALR mutation were younger, had lower white blood cell counts, and experienced less thrombosis during follow-up than those carrying JAK2 V617F mutation, while both patient groups showed similar clinical features and prognosis. In ET patients without JAK2 V617F mutation, CALR mutation did not significantly affect clinical manifestation and prognosis. In conclusion, CALR mutation analysis could be a useful diagnostic tool for ET and PMF in 50% of the cases without JAK2 V617F mutations. The prognostic impact of CALR mutations needs further investigation.

Primary myelofibrosis: risk stratification by IPSS identifies patients with poor clinical outcome

OBJECTIVES: To evaluate whether risk scores used to classify patients with primary myelofibrosis and JAK-2 V617F mutation status can predict clinical outcome. METHODS: A review of clinical and laboratory data from 74 patients with primary myelofibrosis diagnosed between 1992 and 2011. The IPSS and Lille scores were calculated for risk stratification and correlated with overall survival. RESULTS: A V617F JAK2 mutation was detected in 32 cases (47%), with no significant correlation with overall survival. The patients were classified according to the scores: Lille - low, 53 (73.%); intermediate, 13 (18%); and high, 5 (7%); and IPSS- low, 15 (26%); intermediate-1, 23 (32%); intermediate-2, 19 (26%); and high, 15 (31%). Those patients presenting a higher risk according to the IPSS (high and intermediate-2) had a significantly shorter overall survival relative to the low risk groups (intermediate-1 and low) (p = 0.02). CONCLUSIONS: These results emphasize the importance of the IPSS prognostic score for risk assessment in predicting the clinical outcome of primary myelofibrosis patients.

Aspectos diagnósticos, evolutivos y terapéuticos de la mielofibrosis primaria / Diagnostic, evolutionary and therapeutic aspects of primary myelofibrosis

La mielofibrosis primaria se caracteriza por una expansión clonal de la célula madre hematopoyética con una proliferación reactiva no clonal de los fibroblastos y fibrosis de la médula ósea, por lo que ocurre una hematopoyesis extramedular. Por ser una enfermedad rara de la que no se han realizado investigaciones en nuestro medio, se caracterizaron los aspectos diagnósticos, terapéuticos y evolutivos en los pacientes atendidos en el Instituto de Hematología e Inmunología en el período comprendido entre noviembre de 1992 y mayo de 2009. La presentación fue más frecuente en el grupo de mayores de 60 años. El 80 por ciento de los pacientes presentaron síntomas al momento del diagnóstico. Los más frecuentes fueron las molestias en hipocondrio izquierdo, fiebre, sudoración nocturna y pérdida de peso. Los principales hallazgos en el hemograma al debut de la enfermedad, fueron la anemia y la trombocitosis, seguidos de conteos elevados de leucocitos con reacción leucoeritroblástica en el 80 por ciento de los casos. Se observaron cifras elevadas de la LDH en el 78,6 por ciento. En la biopsia de la médula ósea el 60 por ciento se hallaba en estadio prefibrático. Los pacientes fallecidos se encontraban en los grupos de mayor riesgo. La mediana de supervivencia fue de aproximadamente 5,5 años

Primary myelofibrosis is characterized by clonal expansion of hematopoietic stem cell with a non-reactive clonal proliferation of fibroblasts and bone marrow fibrosis, which occurs at an extramedullary hematopoiesis. Since it is a rare disease for which no research has been conducted in our environment, we charcterized the diagnostic aspects, treatment and evolution in patients treated at the Hematology and Immunology Institute during the period between November 1992 and May 2009. The most frequent presentation was in the group older than 60 years. 80 percent of patients had symptoms at diagnosis. The most frequent were the left upper quadrant discomfort, fever, night sweats and weight loss. The main findings in the blood count at this disease onset were anemia and thrombocytosis followed by high leukocyte counts with leukoerythroblastic reaction in 80 percent of cases. There were high levels of LDH 78.6 percent. The bone marrow biopsy was 60 percent pre fibrotic stage. Patients who died were in the highest risk groups. The median survival was approximately 5.5 years

JAK2-positive Philadelphia-negative myeloproliferative neoplasms.

The recent discovery of the JAK2 mutations has rekindled interest in the approach to classic BCR/ABL-negative myeloproliferative neoplasms (MPNs) in terms of both diagnostic evaluation and treatment. However, additional clinical, laboratory and histological parameters play a key role to allow diagnosis and subclassification, regardless of whether JAK2 V617F mutation is present or not. Here are two cases which incidentally presented with splenomegaly and moderate leukocytosis, and were diagnosed as MPN-primary myelofibrosis (PMF) in prefibrotic phase and polycythemia vera (PV), respectively, using revised World Health Organization (WHO) 2008 criteria.

Fibrosis peri radicular post-quirúrgica del raquis lumbar: qué hacer? / Peri radicular fibrosis Post-surgical Lumbar Spine: what to do?

Objetivos: La presencia de sintomatología secundaria a la fibrosis posquirúrgica tras la cirugía de la Hernia de disco y Estenosis de canal es una de las peores noticias tanto para el paciente como para el cirujano. Se hace necesario una prevención de dicha sintomatología (Entre el 2 y el 18 por ciento de los pacientes la presentan tras dicha cirugía), mediante el desarrollo de una barrera física: matriz de colágeno Tipo IV, con una tripe acción A) Función de Hemostasia, B) barrera física por la porosidad, C) función regeneradora por la matriz. Material y Métodos: Se ha realizado un estudio retrospectivo en un total de 600 pacientes intervenidos de cirugía de raquis con abordaje del Canal; 200 pertenecían al grupo control, 400 al grupo Duragen. Tras la cirugía se coloco el duragen tanto en la zona del defecto óseo, como en la zona de revisión de la raíz: Fenestración de anillo fibroso; foraminotomia y sangrado de vasos epidurales como hemostasia residual, de esta manera se crea una barrera física que impide al fibroblasto del músculo poder atrapar a la raíz tras la cicatrización del músculo .además en caso de fístula de LCR la matriz favorece el paso de fibroblastos entre la dos laminas de la dura a través de la matriz y se produce un sellado completo del orificio. El seguimiento mínimo fue de un año y se realizaron controles clínicos y radiológicos de forma seriada. Resultados: Del total de pacientes del grupo control; un 8 por ciento presentaron sintomatología secundaria a fibrosis que requiero tratamiento mediante: nueva cirugía (Fijación Lumbar: artrodesis) o colocación de un neuroestimulador. En el grupo D no se presentaron pacientes con sintomatonología por fibrosis. 0.6 por ciento vs. 8 por ciento. Discusión: La evolución de los pacientes tratados con Duragen obtuvo un mejor resultado al no presentar sintomatología por fibrosis, además en caso de fístula esta quedo sellada. En los casos en los que hubo que reoperar por otros factores: recidiva...

Objective: The symptomatic appearance of post-operative fibrosis following surgery for lumbar disc herniation is bad news for both the patient and the surgeon. A method of preventing this undesired outcome would be of great utility (between 2 and 18 percent of the patients suffer from it after said surgery). Here we report one approach to achieving this outcome, through the development of a physical barrier: a matrix of Type I collagen, with three main attributes: A) Haemostatic function, B) Physical barrier due to its porosity, C) Regenerating function through the matrix. Method: A retrospective investigation was made of 600 patients whom had undergone spinal surgery with canal approach; 200 took part in the control group and 400 took part in the DuraGen group. These procedures involved fenestration of the fibrous ring, foraminectomy and haemostasis of bleeding of epidural vessels. Prior to wound closure, DuraGen was placed both in the area of the bone defect and in the area of the affected nerve root. Thereby creating a physical barrier that prevents fibro tic entrapment of the nerve root. Further, in the event of CSF leakage (fistula) the matrix accomplished complete closure of the dural defect through the process of fibroblast migration and the formation of a new connective tissue sheet continuous with the existing dura. There was a minimum follow-up of Two year that included a series of clinical and radiological exams. Results: From all the control group patients, 8 percent showed secondary symptomatology of fibrosis that required treatment through: new surgery (lumbar fixation: arthrodesis) or placement of a neurostimulator. There were no patients with symptomatology due to fibrosis in the DuraGen group (0.6 percent vs. 8 percent). Discussion: The progress of patients treated with DuraGen showed a better result since there was no symptomatology due to fibrosis. Further, in the event of fistula, the fistula was closed. When there was a need for new surgery...

Juvenile rheumatoid arthritis with myelofibrosis with myeloid metaplasia.

Myelofibrosis with myeloid metaplasia is defined as a myeloproliferative disorder characterized by leukoerythroblastosis, tear drop erythrocytes, extramedullary hematopoesis and varying degree of myelofibrosis. It may be idiopathic or secondary to a large number of conditions. Here is a rare case of myelofibrosis occurring in a patient with juvenile rheumatoid arthritis.

Myelofibrosis and vitamin D deficient rickets--a rare association.

Myelofibrosis is a rare hematological condition in infancy. We report a case of a 6-month-old infant who was diagnosed to have myelofibrosis due to Vitamin D deficient rickets. This rare association of myelofibrosis and rickets is discussed here with a review of relevant literature.

The diagnostic utility of bone marrow trephine biopsies.

The bone marrow examination is invaluable in the diagnosis of certain haematological and non haematological conditions. The diagnosis of haematological disorders is achieved mainly by the examination of peripheral blood and bone marrow aspirate smears. Although bone marrow histology can provide additional information, for many technical reasons, trephines are not so popular and their diagnostic value is overlooked. Our experiences in the role of trephine biopsies in the diagnosis are presented in this article. All the bone marrow biopsies performed at the St. John's Medical College Hospital over the last 12 years (1990-2002) were reviewed The bone marrow biopsies were grouped into 3 categories for analysis. The trephine biopsy is invaluable in cases where the aspirate fails or is a dry tap as in the case of myelofibrosis, focal marrow involvement as in granulomatous lesions, metastatic tumour and lymphomas.

Intracranial myeloid metaplasia in idiopathic myelofibrosis

Extramedullary hematopoiesis is a common finding in idiopathic myelofibrosis and is generally found in the liver, spleen and lymph nodes, but meningeal extramedullary hematopoiesis is very rare. Some diseases may be causes of intracranial masses and diagnosis is difficult. We present a case diagnosed as intracranial and meningeal extramedullary hematopoiesis with idiopathic myelofibrosis inducing serious headache

Myelodysplasie avec myelofibrose un eentite anatomo-clinique particuliere

Myelofibrosis is rarely associated with myelodysplastic syndrome. This association constitute a distinct clinicopathological entity which is difficult to be distinguished from other forms of myelofibrosis. We report six cases of this entity. Patients were aged between 50 and 79 years, with 3 males and 3 females. All these patients had similar clinical features consisting of pancytopenia and absent visceral enlargement. The analysis of bone marrow aspirate was difficult

Linfoma de Hodgkin com apresentação de metástases ósseas e mielofibrose: relato de caso / Hodgkin's disease presenting as bone metastasis and myelofibrisis: case report

Os A.A. descrevem o caso de um paciente de 34 anos com história de dor lombar e febre há dois meses, internado com hipótese de artropatia sosronegativa. Durante a investigação a dor demonstrou-se decorrente de metástases ósseas. Foi procedida a pesquisa do tumor primário, concluindo-se por linfoma de Hodgkin forma esclerose nodular associado à mielofibrose. Discutem-se a dificuldade diagnóstica do caso e a fisiopatologia da associaçào de doenças linfoproliferativas e mielofibrose (au)

Metaplasia mieloide agnogénica: reporte de un caso atípico / Agnogenic myeloid metaplasia: case of report atipic

Se presenta un paciente varón de 19 años de edad, procedente de Papayacu, departamento de Amazonas, con metaplasia mieloide agnogénica (MMA), cuya sintomatología y evolución-con excepción de la fiebre y la esplenomegalia-fueron inusuales, lo cual obscureció el diagnóstico que sólo pudo evidenciarse post-mortem. Paralelamente era portador de una severa desnutrición calórico-proteica y de parasitismo intestinal múltiple, lo que contribuyó a modificar el curso clínico del proceso. Creemos por ello que este caso de metaplasia mieloide agnogénica de presentación muy singular debe ser reportado en la literatura nacional.

Tumor abdominal y púrpura en un lactante de 39 días de vida. Ateneo anatomoclínico del Hospital Garrahan / Clinico-pathological reunion of the Hospital Garrahan

La discusión clínica se basará en el análisis de las principales causas de hepatoesplenomegalia en el período neonatal y en lactactes menores de tres meses de edad. Intentaré excluír rápidamente las afecciones menos frecuentes que cursan con hepatoesplenomegalia, para luego circunscribirme a los diagnósticos diferenciales más probables.

Mielofibrose idiopática / Idiopathic myoelofibrosis

Os autores fazem uma revisäo bibliográfica recente e comparam os dados obtidos aos de prontuários médicos do Serviço de Hematologia do Hospital Brigadeiro - Säo Paulo, no período de 1983 a 1988. Foram analisados oito casos de mielofibrose idiopática (MFI), confirmados através de biópsia óssea de crista ilíaca posterior com agulha de Jamshidi. A faixa etária preodminante foi de 51 a 60 anos, sendo cinco pacientes do sexo masculino e três do sexo feminino. Os sintomas mais referidos foram adinamia, fraqueza e sangramento (seis-oito casos), emagrecimento e dores ósseas (quatro-oito casos). Os sinais encontrados com maior freqüência foram explenomegalia e anemia (sete-oito casos), hepatomegalia (cinco-oito casos) e icterícia (dois-oito casos). O hematoma näo apresentou padräo definido. A maior parte dos casos foram diagnosticados em estádios avançados da doença. O tratamento isolado ou combinado com bussulfan, prednisona, oximetalona e radioterapia esplênica mostrou-se útil para alívio de sintomas abdominais compressivos. A análise retrospectiva dos pacientes con MFI demonstra que essa patologia deve ser obrigatoriamente incluída no diagnóstico diferencial de hepatoesplenomegalia associada a anemia

El medulograma y la biopsia de médula ósea en las leucemias agudas: síndromes mieloproliferativos crónicos y otras enfermedades hematológicas / Medullogram and bone marrow biopsy in acute leukemias, chronic myeloproliferative syndromes and other hematologic diseases

Se le realizaron medulograma y biopsia de médula ósea a 62 pacientes con las siguientes enfermedades agudas (17), mielofibrosis aguda (1), síndromes mieloproliferativos (33) y anemias refractarias (11). La biopsia de médula ósea permitió confirmar el diagnóstico en todos los casos y lo estableció en algunos en los que la muestra de la punción medular fue blanca. Además, mostró diferentes patrones histológicos y de infiltración medular que ayudaron a estadificar las enfermedades y a predecir el pronóstico